Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry is a well known method that offers higher mass resolution, greater mass resolving power, and higher mass accuracy than other known mass analysis methods. The principles of FT-ICR are described in several recent review articles. These review articles include: A. Marshall, C. Hendrickson, G. Jackson, Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: A Primer, Mass Spectrometry Reviews, Volume 17, 1998, pp. 1–35; A. Marshall, Milestones in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Technique Development, International Journal of Mass Spectrometry, Volume 200, 2000, pp. 331–356; T. Wood, Electrospray Ionization Fourier Transform Mass Spectrometry of Macromolecules: The First Decade, Applied Spectroscopy, Volume 53, No. 1, 1999, pp. 18A–36A, and A. Marshall and C. Hendrickson, Fourier Transform Ion Cyclotron Resonance Detection: Principles and Experimental Configurations, International Journal of Mass Spectrometry, Volume 215, 2002, pp. 59–75.
The performance of FT-ICR is achieved through the combination of electric and magnetic fields, and is based upon the principle of ion cyclotron resonance (ICR). Ions in the presence of a uniform static magnetic field are constrained to move in circular orbits in the plane perpendicular to the direction of the magnetic field and are unrestricted (by the magnetic field) to move parallel to the magnetic field direction. The radius of this circular motion is dependent on the momentum of the ions in the plane perpendicular to the magnetic field. The frequency of the circular motion (cyclotron frequency) is a function of the mass-to-charge (m/z) ratio of the ion and the magnetic field strength. Trapping electrodes provide a static electric field, which prevent the ions from escaping along the direction of the magnetic field lines. The ions are confined within the trap. As long as the vacuum is kept high (typically <10−8 to 10−10 mbar), ion/neutral collisions are minimized and the ion trapping duration is maximized.
When the ions are initially trapped, they have an initial low amplitude cyclotron radius defined by their thermal velocity distribution and their initial radial positions. This low amplitude motion is of random initial phase. This state is referred to generally as “incoherent” oscillatory motion. While these ions are trapped, an oscillating electric field can be applied perpendicular to the magnetic field causing those ions having a cyclotron frequency equal to the frequency of the oscillating electric field to resonate. The resonant ions absorb energy from the oscillating electric field, accelerate, gain kinetic energy and move to larger orbital radii. This process, termed “ion excitation”, adds a large amplitude coherent cyclotron motion on top of the low initial thermal amplitude incoherent cyclotron. The net effect is that ions of a given cyclotron frequency, and hence mass, orbit as a packet. When the applied excitation field is switched off, the ions stop absorbing energy and the packet then orbits the chamber at the fundamental cyclotron frequency of the ions that comprise the packet. The ion packet produces a measurable signal by inducing onto nearby electrodes an image-charge that oscillates at the same cyclotron frequency. This charge induces an oscillating current in circuitry attached to the electrodes, and this signal current can be amplified, detected, digitized, and stored in computer memory. The measured signal is typically in the form of a damped sine wave function with the characteristic cyclotron frequency as described above. The mass spectrum is obtained by application of a Fourier transform to the measured time domain induced signal to extract the cyclotron frequencies associated with the various ions. Once the cyclotron frequencies are known, the m/z values are calculated using a modified, two term version of the cyclotron equation that accounts for both the magnetic and electric fields.
The spectral peak width actually achieved by FT-ICR systems is affected by many factors. Principal among these are instrumental factors such as the strength and homogeneity of the magnetic and electric fields. The goal of achieving higher resolving power is typically pursued at the great expense of developing larger, higher-field magnets. Although these instrumental factors are of primary importance, the computational procedures employed to obtain spectra from the acquired time domain data can also have a significant affect on the achieved peak width. Many different approaches to extraction of frequency from the time domain data have been explored. However, the most common procedure is to perform an apodization (or “windowing”) to suppress the broad base of the true frequency domain peak(s) that correspond to the true shape of the time-domain data, followed by zero fill and fast Fourier transform (FFT) to yield the desired frequency spectrum.
As long as the magnetic field in which ions are confined is relatively homogeneous, the various frequencies in the generated frequency spectrum accurately represent the ion cyclotron frequencies. Accordingly, the mass-to-charge (m/z) ratio of the various ions from a given sample can be measured with high accuracy.
However, the resolving power of conventional FT-ICR systems is not optimized because each of the complex components of the corresponding frequency spectrum derived from the measured time domain detection data set generally includes a mixture of the absorption and dispersion modes. This is because factors such as the time delay between the excitation and detection events, as well as temporally dispersed excitation events (e.g. frequency-sweeps) result in continuous variation of phase with frequency in the time domain detection data set. The mixing of absorption and dispersion modes makes the resulting peak shapes highly asymmetrical. FIG. 1 shows a conventional excitation and detection sequence showing a time delay prior to start of detection and digitation to avoid excitation induced detection preamplifier saturation.
Conventional FT-ICR systems utilize a magnitude mode spectral display to restore peak symmetry at the expense of spectral resolution that would be available from a pure absorption mode spectrum. Alternatively, some form of phase correction is sometimes applied to restore a pure absorption-mode peak shape. However, available methods for phase correction have been limited to narrow spectral bandwidth and require manual data manipulation to “tune” the correction process.